tbuckley/cabot-search huggingface dataset:
Publication trend for COVID-19 in Urology: What have Urologists researched in a year and a half of the Pandemic?
Authors: F. Crocerossa, W. Visser, U. Carbonara, U.G. Falagario, S.D. Pandolfo, C. Imbimbo, A. Klausner, F. Porpiglia, R. Damiano, F. Cantiello, R. Autorino
Journal: European Urology (2022)
Cancer of unknown primary site: A population-based analysis of demographics and all-cause mortality.
Authors: Bharath Ganesh, Bhanusowmya Buragamadagu, Bohdan Baralo, Matthew Stewart, Rajesh Thirumaran
Journal: Journal of Clinical Oncology (2022)

e18518 Background: Cancer of unknown primary site (CUP) is an entity that is defined by the presence of an occult primary site despite sufficient workup. Prior analyses have concluded that CUP has a poor overall prognosis. This study aims to examine a recent US cohort of patients with CUP, with a focus on discerning demographic characteristics and common causes of mortality. Methods: Patients with CUP were identified from the Surveillance, Epidemiology, and End Results (SEER) database, a large US population-based cancer registry (using SEER*Stat 8.3.4 software). Patients of all ages with cancers diagnosed between 2010-2014 were included in the study. Patients with CUP were identified by ICD-O-3 code C80.9 (‘Unknown Primary Site’). Data were extracted for adenocarcinomas and squamous cell carcinomas separately. Ill-defined and rarer histologies like ‘carcinoma, NOS’ and neuroendocrine tumors were excluded from this study. Results: The number of cases identified was 9,683 adenocarcinomas and 3,758 squamous cell carcinomas, totaling 13,441 cases that met eligibility. The median age at diagnosis was 71 +/- 13.0 years. Sex distribution was nearly equal, with males accounting for 50.8% of cases, and females 49.2%. Most patients were of ‘White’ race (81.6%), and the remainder comprised ‘Black’ (10.8%), ‘Other’ (American Indian, AK Native, Asian/Pacific Islander) (6.7%), and ‘Unknown’ (0.9%). Adenocarcinoma and its subtypes were the most common histological type reported (71.7%). Notable solid organ metastatic sites irrespective of tumor histology were bone (3.0%), brain (0.6%), liver (5.1%), and lung (0.9%). The median survival of the overall population was 2.0 months. 3,195 patients were alive at the end of the study period. Death from any cancer unsurprisingly accounted for the vast majority of mortality (87.0%). Most non-cancer deaths were caused by cardiovascular disease (4.6%) and infections (1.2%). Conclusions: CUP remains a disease with dismal prognosis. Our study characterizes the demographics and most common causes of death in patients with CUP. Patients who were diagnosed with CUP tended to be elderly, White individuals of either sex. Most patients with CUP died from their cancer, with a median survival duration of two months. Further research is required to evaluate newer treatment modalities such as targeted therapy and immunotherapy in order to improve patient outcomes.
MEDB-62. Disease-associated KBTBD4 mutations in medulloblastoma elicit neomorphic ubiquitylation activity to promote CoREST degradation
Authors: Zhuoyao Chen, Rafael Ioris, Stacey Richardson, Ava Van Ess, Iolanda Vendrell, Benedikt Kessler, Francesca Buffa, Luca Busino, Steven Clifford, Alex Bullock, Vincenzo D'Angiolella
Journal: Neuro-Oncology (2022)

Abstract Genomic studies in medulloblastoma have identified distinct disease subgroups: wnt/wingless (WNT), sonic hedgehog (SHH), and non-WNT/non-SHH, comprising group 3 and group 4. Alterations in WNT and SHH signalling form the pathogenetic basis for their subgroups, whereas those for non-WNT/non-SHH tumours remain largely elusive. Recent analyses have revealed recurrent in-frame insertions in the E3 ubiquitin ligase adaptor Kelch Repeat and BTB Domain Containing 4 (KBTBD4) in cases of group 3 and group 4 medulloblastoma. Critically, group 3 and 4 tumours with KBTBD4 mutations typically lack other gene-specific alterations, such as MYC amplification, indicating KBTBD4 insertion mutations as the primary genetic driver of these malignancies. Delineating the role of KBTBD4 mutations in medulloblastoma thus offers significant opportunities to understand its pathogenesis and exploit underpinning mechanisms therapeutically, however their function is currently unknown. Here, we show a novel mechanism in cancer pathogenesis whereby indel mutations in KBTBD4 drive its recognition of neo-substrates for degradation. We observe that KBTBD4 mutants promote the recruitment and ubiquitylation of the REST Corepressor (CoREST), which forms a complex to modulate chromatin accessibility and transcriptional programmes. The degradation of CoREST promoted by KBTBD4 mutations diverts epigenetic programmes inducing significant alterations in transcription to promote increased stemness of cancer cells. Transcriptional analysis of &amp;gt;200 human group 3 and 4 medulloblastomas by RNA-seq, highlights the presence of CoREST and stem-like signatures in tumours with KBTBD4 mutations, which extend to a further sub-set of non-mutant tumours, suggesting CoREST alterations as a novel pathogenetic mechanism of wide relevance in group 3 and 4. Our findings uncover KBTBD4 mutation as a novel driver of epigenetic reprogramming in non-WNT/non-SHH medulloblastoma, establishes a novel mode of tumorigenesis through gain-of-function mutations in ubiquitin ligases (neo-substrate recruitment) and identifies both mutant KBTBD4 and CoREST complexes as new druggable targets for improved tumour-specific therapies.
Oncologic outcomes of primary retroperitoneal lymph node dissection (RPLND) for stage II seminoma: Indiana University experience.
Authors: Isamu Tachibana, Andre Alabd, Alex Piroozi, Mohammad Mahmoud, Sean Kern, Yan Tong, Timothy A. Masterson, Nabil Adra, Richard Foster, Nasser H. Hanna, Lawrence H. Einhorn, Clint Cary
Journal: Journal of Clinical Oncology (2022)

e17012 Background: Stage II seminoma is typically treated with radiotherapy or chemotherapy based on NCCN guidelines. Primary RPLND has demonstrated efficacy as first-line therapy for retroperitoneal (RP)-only disease. Our aim was to study recurrences of patients undergoing primary RPLND for Stage IIa or IIb seminoma to identify clinicopathologic factors affecting outcomes. Methods: Using our prospectively maintained database, we identified patients that had primary RPLND for seminoma from 2014-2021. All patients had at least 6 months of follow up. Patients were clinical stage IIa or IIb at the time of surgery and underwent open RPLND. We used Kaplan-Meier analysis for recurrence free survival (RFS) and compared clinicopathologic factors. Results: We identified 67 patients that underwent RPLND for RP only seminoma. Table shows the clinical characteristics of patients experiencing recurrences (median follow up - 22.4 months) and excludes 2 patients that had adjuvant chemotherapy. The 2-year RFS rate was 80.2%. Eleven patients (16.4%) experienced recurrences. Kaplan Meier analysis demonstrated improved survival in patients that had an RPLND after 12 months of surveillance (p = 0.02). Fifty-six patients were presumably cured with surgery alone at time of last follow-up. No patients died of testis cancer. One patient had a recurrence within the surgical field. Two patients had contralateral recurrences that may have been cured with bilateral RP template dissection. Seven patients that had a bilateral template dissection had disease on the contralateral side, of which 4 patients had visible nodes on pre-operative scans. In total, 9 out of 67 patients had disease on the contralateral side suggesting that bilateral RP template could confer higher cure rates. Recurrences were successfully treated with BEPx3 (9 pts), Redo RPLND then BEPx3 (1 pt), BEPx3 then High Dose chemotherapy (1 pt), and EPx4 (1 pt). Conclusions: Primary RPLND for low volume RP disease is effective with over 80% chance of surgical cure. Recurrences were cured almost exclusively with induction chemotherapy. Patients with delayed RP only recurrences had improved surgical success. Further investigation in larger trials may help standardize bilateral templates in seminoma and surveillance protocols in the post-operative setting. [Table: see text]
Transcriptomic profiling of patients (pts) with de-novo metastatic castration-sensitive prostate cancer (DN-mCSPC) versus those with mCSPC that have relapsed from prior localized therapy (PLT-mCSPC).
Authors: Nicolas Sayegh, Beverly Chigarira, Edgar Javier Hernandez, Taylor Ryan McFarland, Haoran Li, Kamal Kant Sahu, Nishita Tripathi, Shruti Adidam Kumar, Blake Nordblad, Divyam Goel, Clara Tandar, Mark Yandell, Roberto Nussenzveig, Deepika Sirohi, Benjamin L. Maughan, Umang Swami, Neeraj Agarwal
Journal: Journal of Clinical Oncology (2022)

5080 Background: Pts with DN-mCSPC have been reported to experience worse prognosis and outcomes compared to those with PLT-mCSPC. We hypothesized that gene expression profiling of pre-treatment primary prostate tumors from PLT-mCSPC pts would be distinct from those with DN-mCSPC. Methods: Eligibility criteria: histologically confirmed mCSPC and available RNAseq profiling performed by a CLIA certified lab using primary prostate biopsies collected prior to start of treatment. Pts were categorized into two cohorts: PLT-mCSPC versus DN-mCSPC. The DEseq2 pipeline was used to analyze differentially expressed genes between the groups. The data included the Log2 fold change, Wald-Test p-values, and Benjamini-Hochberg adjusted p-values for each differentially expressed gene. These results were subjected to Gene Set Enrichment software analysis (GSEA) in order to identify pathways enriched in each cohort. All bioinformatic analysis was undertaken using R v4.2. Results: Ninety-seven (97) patients met eligibility (52 PLT, 45 de novo). Characteristics of the overall eligible pts: median age = 65, median baseline PSA = 12.6, Gleason score ≥8 = 71%, and high volume of disease = ̃30%. Differential expression and pathway enrichment between cohorts: upregulation of cell-cycle signaling pathways (G2-M checkpoint, E2F) in pts with DN-mCSPC, and upregulation of androgen signaling and immune pathways (inflammatory response, NFKB-mediated TNF-alfa signaling) in pts with PLT-mCSPC (Table). Conclusions: These hypothesis-generating data, upon external validation, may provide the rationale for personalized therapy in men with mCSPC, such as the use of CDK4/6 inhibitors in addition to standard of care intensified ADT in men with DN-mCSPC. [Table: see text]
Amivantamab in patients with NSCLC with MET exon 14 skipping mutation: Updated results from the CHRYSALIS study.
Authors: Matthew Krebs, Alexander I. Spira, Byoung Chul Cho, Benjamin Besse, Jonathan W. Goldman, Pasi A. Janne, Zhiyong Ma, Aaron Scott Mansfield, Anna Rachel Minchom, Sai-Hong Ignatius Ou, Ravi Salgia, Zhijie Wang, Casilda Llacer Perez, Grace Gao, Joshua C Curtin, Amy Roshak, Robert W. Schnepp, Meena Thayu, Roland Knoblauch, Chee Khoon Lee
Journal: Journal of Clinical Oncology (2022)

9008 Background: Amivantamab, a fully human bispecific antibody targeting epidermal growth factor receptor (EGFR) and MET, is approved for the treatment of non-small cell lung cancer (NSCLC) with EGFR exon 20 insertion after prior platinum-based chemotherapy. Given its bispecific nature, amivantamab is being explored in patients (pts) with primary MET exon 14 skipping mutation (METex14) in the MET-2 cohort of the CHRYSALIS study. Methods: CHRYSALIS (NCT02609776) is an ongoing phase 1 dose escalation/dose expansion study of amivantamab in pts with advanced NSCLC. Pts with primary METex14 whose disease progressed on or who declined current standard of care therapy were treated with amivantamab 1050 mg (pts &lt;80 kg) or 1400 mg (pts ≥80 kg) weekly in cycle 1 and biweekly thereafter. Response was assessed by investigators using RECIST v1.1. Results: As of 2 Dec 2021, 43 pts with METex14 had received amivantamab. Median age was 70 y (range, 43-88), 58% were women, median prior lines of therapy was 2 (range, 0-10) [eg, crizotinib (n=13), capmatinib (n=11), tepotinib (n=5), anti-MET antibody (n=1)], and 23% had history of brain metastases at baseline. In 36 pts with ≥1 postbaseline disease assessment, median duration of follow-up was 5.8 months (range, 0.3-15.8); 6 pts had no prior treatment, 11 had no prior MET inhibitor, and 19 had a prior MET inhibitor. Overall response rate was 33% (50% [3/6] in treatment-naïve pts, 46% [5/11] in pts with no prior MET inhibitor, and 21% [4/19] in pts with prior MET inhibitor therapy). Clinical benefit rate was &gt;54% regardless of prior treatment (Table). Median duration of response (DOR) was not reached (range, 2.1-12.2 months); 67% (8/13) had DOR ≥6 months. Ten of the 12 responders remain on treatment (6.0-14.4 months) with ongoing responses; 2 discontinued after 2 and 12 months, respectively. Safety profile was consistent with previously reported experience of amivantamab (Sabari 2021 JTO 16(3):S108-109). Treatment-related adverse events leading to dose reduction or discontinuation occurred in 3 pts, each. Conclusions: Amivantamab demonstrates anti-tumor activity in primary METex14 NSCLC including after prior MET inhibitor treatment. Enrollment is ongoing and updated data will be shown. Clinical trial information: NCT02609776. [Table: see text]
Outcomes of anti–PD-(L)1 therapy with or without chemotherapy (chemo) for first-line (1L) treatment of advanced non–small cell lung cancer (NSCLC) with PD-L1 score ≥ 50%: FDA pooled analysis.
Authors: Oladimeji Akinboro, Jonathon Joseph Vallejo, Erica C. Nakajima, Yi Ren, Pallavi Shruti Mishra-Kalyani, Erin A. Larkins, Paz J. Vellanki, Nicole Lauren Drezner, Luckson Noe Mathieu, Martha Boeri Donoghue, Shenghui Tang, Richard Pazdur, Julia A. Beaver, Harpreet Singh
Journal: Journal of Clinical Oncology (2022)

9000 Background: FDA-approved 1L treatment options for patients with PD-L1-high advanced NSCLC (PD-L1 score ≥50%) include IO ± chemo (± anti-angiogenics) but it is unclear if chemo substantially improves efficacy outcomes when added to IO in this patient population. Methods: Data was pooled from 12 randomized controlled trials that investigated anti-PD-(L)1 regimens ± chemo for the 1L treatment of patients with advanced NSCLC. PD-L1 score was defined as the proportion of tumor cells stained by the assay and analysis was conducted for patients with tumor PD-L1 score ≥50%. OS, PFS, and ORR were compared between chemo-IO and IO alone via a pooled analysis. Median survival times were estimated using Kaplan-Meier methods. Hazard ratios were estimated using Cox proportional hazards models stratified by trial; odds ratios were estimated using a logistic regression model with trial as a covariate. All analyses were adjusted for age, sex, race, ECOG, histology and smoking status. Results: A total of 3,189 patients with NSCLC and PD-L1 score ≥50% were identified for this analysis. Baseline characteristics were: 38% ages 65-74 years and 11% ages ≥75 years; 69% male; 80% White; 66% ECOG ≥1; and 89% former/current smokers. Median OS in the pooled chemo-IO ( N=455) and IO-only ( N=1,298) arms was 25.0 vs 20.9 months (HR 0.82; 95% CI: 0.62, 1.08); median PFS was 9.6 vs 7.1 months, respectively (HR 0.69; 95% CI: 0.55, 0.87). ORR was higher with chemo-IO than with IO alone (61% vs 43%; Odds ratio 1.2, 95% CI: 1.1, 1.3). Conclusions: This exploratory, hypothesis-generating pooled analysis suggests that most subgroups of patients with advanced NSCLC with PD-L1 score ≥50% receiving FDA-approved chemo-IO regimens may have OS and PFS outcomes that are comparable with or better than IO-only regimens. Patients ≥75 years of age receiving chemo-IO may not have improved outcomes over IO. These results support shared decision-making that balances potential benefits and risks of adding chemo to IO regimens based on patient factors that may impact tolerability. [Table: see text]
The impact of population-based EGFR testing in metastatic non-small cell lung cancer in Alberta.
Authors: Darren R Brenner, Dylan E. O'Sullivan, Tamer N. Jarada, Amman Yusuf, Devon J Boyne, Cheryl A Mather, Adrian Box, Donald Morris, Winson Y. Cheung, Imran Mirza
Journal: Journal of Clinical Oncology (2022)

e21139 Background: While Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors have been shown to be effective in phase III randomized trials, the value of targeted therapies have been challenging to evaluate at the population level. We examined the impact of population-level EGFR testing and treatment on survival outcomes among metastatic Non-Small Cell Lung Cancer (NSCLC) patients. Methods: Real-world, population-level data were collected from all de novo metastatic non-squamous NSCLC patients in Alberta, Canada from 2004 to 2020. EGFR testing data were collected through Alberta Precision Laboratories using various text mining approaches. Differences in survival rates and overall survival (OS) pre (2004-2012) and post-initiation (post) (2013-2019) testing periods were evaluated using interrupted time series analyses. The impact of testing and subsequent treatment weas evaluated using multivariable Cox Proportional Hazards models. Results: In total, 4,578 metastatic NSCLC patients with a confirmed non-squamous cell carcinoma histology were diagnosed pre- EGFR testing and 4,457 patients were diagnosed post- EGFR testing (2013-2019). Among patients diagnosed in the pre- EGFR testing period, the 6-month, 1-year, and 2-year survival probabilities were 0.39 (95% CI: 0.38-0.41), 0.22 (95% CI: 0.21-0.23), and 0.09 (95% CI: 0.08-0.10), while the survival probabilities for patients diagnosed in the post- EGFR testing period were 0.45 (95% CI: 0.43-0.46), 0.29 (95% CI: 0.27-0.30), and 0.16 (95% CI: 0.15-0.1 7), respectively. After adjusting for baseline patient and clinical characteristics, OS in the post- EGFR period was significantly improved compared to the pre- EGFR period (HR: 0.81; 95% CI: 0.78-0.85). In the post-EGFR period, among patients who were treated with systemic therapy, those tested for an EGFR mutation had significantly greater survival than patients who were not tested HR of 0.81 (95% CI: 0.70-0.95). Conclusions: These results show the considerable impact of population-based molecular testing and subsequent targeted therapies on survival among advanced NSCLC patients. The estimates here can be used in future studies to evaluate the population-level cost-effectiveness of testing and treatment.
Climate-smart actions in the operating theatre for improving sustainability practices: A systematic review
Authors: B. Pradere, R. Mallet, A. De La Taille, F. Bladou, D. Prunet, S. Beurrier, F. Bardet, X. Game, G. Fournier, E. Lechevallier, P. Meria, X. Matillon, T. Polguer, N. Abid, B. De Graeve, D. Kassab, A. Mejean, V. Misrai, U. Pinar
Journal: European Urology (2022)
Pre-surgery blood levels of leucine-rich alpha-2-glycoprotein 1 identify patients with a high risk of progressing to castration-resistant prostate cancer
Authors: I.J. Guldvik, S. Sivanesan, H. Ramberg, P. Tennstedt, C.E. Nunes-Xavier, B. Katz, A. Svindland, J.I. Lopez, P. Rustøen Braadland, C.A. Dunne, T. Schlomm, V. Berge, L.M. Eri, W. Lilleby, I.G. Mills, K. Austlid Taskén
Journal: European Urology (2022)
Using multiomics analysis to examine prognostic biomarkers for patients with squamous cell lung carcinoma treated with neoadjuvant therapy of camrelizumab combined with Apatinib.
Authors: Jinliang Wang, Di Lu, Jinzhao Zhai, Zhibo Zhang, Xiang Yan, Fan Zhang, Lijie Wang, TAO Haitao, Fang Yuan, Xiaoyan Li, Xiaoyu Zhi, Xiangwei Ge, Yi Hu, Wenhao Zhou, Haitao Luo
Journal: Journal of Clinical Oncology (2022)

e20563 Background: Immune checkpoint inhibitor (ICI) combined with targeted therapy as a neoadjuvant therapy has been applied to the treatment of squamous cell lung carcinoma (SCLC). However, biomarkers to predict the response are unclear. Methods: 26 SCLC patients treated with neoadjuvant therapy of camrelizumab combined with apatinib were enrolled. Pretreatment samples of these patients were performed with whole-exome sequencing, RNA sequencing, TCR sequencing and IHC of PD-L1 expression. Peripheral blood at different timepoints were collected and analyzed with ctDNA sequencing. Results: At baseline, tumor mutation burden was found to be associated with clinical benefit. For patients with HLA intact, tumor neoantigen burden are significantly increased in the benefited group compared with non-benefited group. Transcriptome analysis revealed that regulatory T cells were significant higher in non-benefited group. In addition, diversity of dominate T-cell receptor repertoire was found to be associated with clinical benefit. Post-treatment, the levels of ctDNA decreased in the benefited group. Conclusions: In this study, we comprehensively analyzed the genomic, tumor microenvironment and serum biomarkers in SCLC patients treated with ICI combined with targeted therapy, and found that TMB, regulatory T cells and change of ctDNA levels were associated with the clinical benefit. In addition, the combination of HLA status and TNB could further distinguish responders.
A preliminary review of adoption of new HCPCS codes for NGS in CMS claims.
Authors: Dave Smart, Wendy Moore, Susanne Munksted Fosvig, Kenneth Joel Bloom
Journal: Journal of Clinical Oncology (2022)

e13522 Background: Adequate reimbursement is considered a prerequisite for adoption of new diagnostic technologies that facilitate patient access to better treatments. Detailed longitudinal investigation of the adoption of new HCPCS codes and the factors influencing it are scarce, although the availability of large-scale claims databases should facilitate such studies. We examined claims for three CPT codes used for next generation sequencing (NGS): 81445, 81450 and 81455 in a large database of claims data from CMS and attempted to correlate presumptive drivers of test adoption such as coverage decisions and payments with test volume. Methods: CMS claims data were accessed using CMS’ Virtual Research Data Center (VRDC) under data use agreement 50486. Any claim with a CPT code of 81445, 81450 or 81455 was extracted from the data and analysed using SAS Enterprise Guide with results summarised in Microsoft Excel. Data relating to national/local coverage determinations were located by internet searches. Results: Test volumes for all 3 codes showed significant variability, including a large decrease around Q1-2 of 2020, likely due to the COVID-19 pandemic. Utilization of the 3 CPT codes varied by patient diagnosis. Details of the top 5 diagnoses for each CPT are given in the Table. The top 30 diagnoses for each CPT code accounted for 80.33%-88.45% of patients. Conclusions: Utilisation of NGS testing from 2016-2021 was highly variable, confounding attempts to match potential drivers to changes in monthly test volumes. A relatively small number of conditions accounted for &gt;80% test use. Increased use of 81445 and 81450 from 2019 onwards may be related to CMS LCD issued in March 2018, suggesting that it can take 8-9 months or more for a LCD to filter through to testing practice. Decreases in test volume around March 2020 coincide with decreased patient presentation and testing for cancer because of the COVID-19 pandemic indicating that factors beyond reimbursement can significantly affect test use. Changes in reimbursement or adoption of proprietary lab analysis (PLA) codes covering specific NGS tests may have caused the drop in test volumes in the latter half of 2021. This study demonstrates that determination of factors affecting adoption of a test technology can be problematic due to wide variation in claims over a relatively short space of time. However, determination of these factors is important as they ultimately affect patient access to testing and potentially to therapy. [Table: see text]
Role of target biopsy, perilesional biopsy, and random biopsy in the detection of clinically significant prostate cancer by mpMRI-guided transrectal ultrasound fusion biopsy in biopsy naïve patients with positive mpMRI: Less is not more
Authors: G. Novara, G. Zecchini, A. Pellizzari, G. Ferraioli, M. Carlesso, G. La Bombarda, A. Lauro, C.S. Lacognata, M.P. Gardiman, M. Mancini, A. Morlacco, F. Dal Moro
Journal: European Urology (2022)